WO1999009407A1

WO1999009407A1 - Condition detector

Info

Publication number: WO1999009407A1
Application number: PCT/GB1998/002405
Authority: WO
Inventors: Peter Alfred Payne; Krishna Chandra Persaud; Allan John Syms
Original assignee: Osmetech Plc
Priority date: 1997-08-14
Filing date: 1998-08-10
Publication date: 1999-02-25
Also published as: GB9717209D0

Abstract

There is disclosed a method for detecting the occurrence of a condition in a female patient comprising the steps of: obtaining a sample of gaseous or volatile substances from the vaginal region of the patient; detecting said gaseous or volatile substances with a gas sensing device; and correlating the detection of said gaseous or volatile substances with the occurrence of the condition.

Description

CONDITION DETECTOR

This invention relates to methods and apparatus for detecting the occurrence of conditions in a female patient, with particular, although by no means exclusive, reference to vaginal conditions such as cervical cancer.

Cervical cancer is a relatively common condition, and, accordingly, in the UK a great deal of effort has been spent in providing regular screening for the condition. However, the existing tests are not always reliable and, furthermore, are rather intrusive and uncomortable for the patient. It would be desirable to provide a more accurate test. Furthermore, it would be desirable to provide a less intrusive test in which steps involving contact with the body could be easily performed by the patient herself.

The present invention addresses the aforementioned considerations, as well as providing methods and apparatus for the convenient detection of numerous conditions in a female patient.

According to a first aspect of the invention there is provided a method for detecting the occurrence of a condition in a female patient comprising the steps of:

obtaining a sample of gaseous or volatile substances from the vaginal region of the patient;

detecting said gaseous or volatile substances with a gas sensing device; and

correlating the detection of said gaseous or volatile substances with the occurrence of the condition. The sample may be obtained by applying sampling means to the vaginal region of the patient and transporting said sampling means to a gas sampling arrangement adapted to introduce gaseous or volatile substances emanating from said sampling means to said gas sensing device. The sampling means may comprise a tampon, swab or means adapted to fit on the cervical cone.

Alternatively, the gas sensing device may be positioned in the vicinity of the vaginal region of the patient and said gaseous or volatile species sampled directly by the device. The gas sensing device may be integrated into a pair of panties or the like, or into a tampon or the like.

The gas sensing device may comprise at least one semiconducting organic polymer gas sensor.

The gas sensing device may comprise an array of gas sensors.

The condition detected may be cervical cancer.

The condition detected may be ovarian or uterian cancer.

The condition detected may be a vital infection, which may comprise infection with human papilloma virus, cytomegalovirus, a sexually transmitted disease (STD) or human immuno deficiency virus (HIV).

The condition detected may be associated with oestrus.

The condition detected may be a yeast infection, which may comprise infection with chlamydia. According to a second aspect of the invention there is provided a gas sensing system adapted to detect the occurrence of a condition in a female patient comprising:

a gas sampling device; and sampling means for obtaining a sample of gaseous or volatile substances from the vaginal region of the patient and introducing said sample to said gas sensing device.

The gas sensing device may be adapted to be positioned in the vicinity of the vaginal region of the patient and to sample directly the gaseous or volatile species. The gas sensing system may be integrated into a pair of panties or the like, or into a tampon or the like.

The gas sensing device may comprise at least one semiconducting organic polymer gas sensor. The detection of gaseous or volatile species may be indicated by a variation in the colour of the semiconducting organic polymer or polymers.

The gas sensing device may comprise an array of gas sensors.

Methods and apparatus in accordance with the invention will now be described with reference to the accompanying Figures, in which:-

Figure 1 shows an apparatus for detecting the occurrence of a condition;

Figure 2 shows two embodiments of sampling means; and

Figure 3 shows a sparging device. The invention provides a method for detecting the occurrence of a condition in a female patient comprising the steps of:

detecting said gaseous or volatile substances with a gas sensing device, and

correlating the detection of said gaseous or volatile substances with the presence of the condition.

Thus, it is possible to recognise the onset of, for example, cervical cancer by detecting certain gases and vapours associated with the condition. The test provided by the present invention has the advantage of being less intrusive, discomforting and embarrassing for the patient, since the patient herself can easily obtain the required sample. It should be noted that many other conditions may be detected using the methods and apparatus of the present invention. For example, the detection of ovarian or uterian cancer, viral infections such as infection with human papilloma virus, cytomegalovirus, a STD or HIV, conditions associated with oestrus, and yeast infections such as infection with chlamydia, are within the ambit of the present invention. The detection of conditions associated with oestrus includes pregnancy testing and fertility monitoring. The detection of bacterial infection, such as bacterial vaginosis is within the scope of the invention, although it is noted that International Publication WO 95/33848 discloses the detection of bacteria er se by monitoring characteristics gases or volatiles. The present invention provides for the detection of non-bacterial conditions.

Furthermore, it is possible to use the methods and apparatus of the present invention to follow the course of a condition without recourse to expensive pathology laboratory time and equipment. The effects of a course of medication can also be monitored.

In one embodiment, the sample is obtained by applying sampling means to the vaginal region of the patient and transporting the sampling means to a gas sampling arrangement adapted to introduce gaseous or volatile substances emanating from the sampling means to the gas sensing device. The application of the sampling means can be performed by the patient herself, or by a medical practitioner (with minimal discomfort and inconvenience). The sampling means may be sealed in a suitable gas- tight container for transportation to the gas sensing device, shown in Figure 1 , which might be situated, for example, in a pathology laboratory. The sampling means 10 is introduced to a gas sampling arrangement 12. Numerous forms of gas sampling arrangements are known in the art - essentially, the purpose is to create a headspace of gases and vapours above the swab or tampon 10, and to transport the gases and vapours to the gas sensing device 14, usually entrained in a flow of an inert gas. The output from the gas sensing device 14 is analysed by a computer 16, which also controls the overall operation of the device 14 and sampling arrangement 12.

The sampling means may comprise a tampon, a swab or means adapted to fit on the cervical cone, i.e. a variant on the so-called "cap". Figure 2a shows in cross section an embodiment of a tampon 20, having an outer layer 22 of a porous material, a semi-permeable membrane layer 24 (to exclude water) and a central pad 26 of an absorbent material. Figure 2b shows an embodiment of a "cap" type sampling means 28 having an absorbent inner layer 30 and an impermeable outer layer 32. The "cap" 28 is adapted to fit on the cervical cone 34 with minimal discomfort. An advantage with the tampon and cap sampling means is that sampling can take place over an extended period with relatively little discomfort to the patient. Figure 3 shows a portion of a gas sampling arrangement comprising a "sparging" device 36. The sampling means 10 is disposed in the sparging device 36 and a carrier gas is flowed over the sampling means 10, thereby entraining gases and volatile species in the gas flow. The carrier gas enters the sparging device 36 via an inlet port 38 and exits via an outlet port 40, thereafter being introduced to the gas sensing device. In a variation, a liquid or solution might be introduced to the sparging device 36 in order to assist in the extraction of volatile species or even to chemically modify certain species. An example is treatment with an alkaline solution in order to produce the emission of amines.

A performed form of gas sensing device 14 comprises at least one semiconducting organic polymer (SOP) gas sensor. Examples of suitable, gas sensitive, SOPs include heteroaromatic polymers such as polypyrrole, polyindole and various substituted variants. The applicants produce commercially a range of gas sensing devices which utilise an array of SOPs. Further details concerning the choice of SOPs, their manufacture, methods for interrogating them and data analysis can be found, for example, Gardner J W and Bartlett P N, Sensors and Actuators B, 18-19 (1994) 211-220; Persaud K C, Bartlett J G and Pelosi P, in "Robots and Biological Systems : Towards a new bionics?", Eds. Dario P, Sandini G and Aebisher P, NATO ASI Series F : Computers and Systems Sciences 102 (1993) 579 and references therein; International Publications WO 96/00383 and WO 96/00384.

Typically an array of SOPs having broad and overlapping sensitivities is employed. However, it is possible to use a single SOP gas sensor in conjunction with a suitable interrogation technique such as applying ac electrical signal to the sensor or a suitable time varying electrical signal accompanied by a time-to-frequency domain transformation (see International Publication WO 97/18467 and British Patent GB 2 203 553). Neural network algorithms are commonly employed for data analysis purposes which, owing to the nature of the data, is usually a pattern recognition problem. An advantage with neural networks is their flexibility. However, simplified data analysis methods may be applicable to devices which are specifically adapted to recognise the occurrence of a single condition. It is advantageous to compile a database representing the gaseous signature of a "normal" population and to compare the odour obtained from the patient with these "control" responses in order to detect abnormalities. The detection of a condition may be based on the intensities of the sensor responses as well as the patterns produced by them.

Other forms of gas sensing device are within the scope of the invention, such as arrays of metal oxide semiconductor gas sensors, SAWS or quartz resonators, or combinations thereof, or forms of gas chromatography .

In another embodiment, the gas sensing device is positioned in the vicinity of the vaginal region of the patient and the gaseous or volatile species are sampled directly by the device. The gas sensing device may be integrated into a pair of panties or the like, in which instance the gas sensors would advantageously be incorporated in a gusset type arrangement. Alternatively, the gas sensing device may be integrated into a tampon. The tampon can be provided with a soft, gas permeable material, such as gauze, as an outer layer. The gas sensor(s) and any associated sensor interrogation functions can be located in the main body of the tampon. SOP gas sensing devices are advantageous in this regard because sensors of relatively small physical dimensions can be readily produced.

These direct sampling embodiments may act purely as data storage devices, with data being downloaded subsequently onto a computer for analysis. Alternatively, they may be provided with means adapted to indicate that the presence of the condition has been detected. One way of doing this is to employ semiconducting organic polymers that change colour on exposure to various gases (the colour change is associated with reduction and oxidation of the polymer - the same physical processes that affect conductivity). In this way, the presence or absence of a desired condition could be indicated by the colour of a gas sensor, or by a colour combination of an array of sensors.

The apparatus might incorporate other sensors, such as pH and temperature sensors, together with the gas sensing device. pH and temperature are important diagnostic conditions, and will probably affect the response of the gas sensing device itself and/or the nature of the species detected.

The precise identities of the characteristic gases and volatile species and the mechanisms for producing them are not, at the present time, well understood. Cancerous conditions are, in some cases, associated with oncogenes which, it is believed, produce proteins very similar in function to normal mammalian regulatory proteins except that they are expressed inappropriately, leading to abnormal growth and differentiation. Many oncogene products are known to encode protein kinases which phosphorylate certain proteins. This reaction then triggers abnormal cellular effects, such as cell division, which will result in a large number of metabolic changes which will potentially produce species detectable in the gas phase. Such metabolic changes include changes in local chemical mediators such as small peptides, amino acid derivatives and fatty acid derivatives, changes in neuro transmitters and changes in various hormones and their effects.

Example

A confidential study detecting bacterial vaginosis was performed analysing vaginal swabs obtained from sixty eight women attending a genitourinary clinic. The patients were tested using standard clinical criteria for the occurrence of bacterial vaginosis. Additionally, a high vaginal swab was taken and placed directly into a sampling pouch which was sealed and sent for analysis. The pouch was unsealed and attached to a header which is part of a commercially available gas sensing device based on SOPs and manufactured by AromaScan pic, Crewe, Cheshire, UK. The pouch was inflated, detached from the header, conditioned at 37 °C for 30 minutes, and then attached to the sampling part of the AromaScan device for analysis. The headspace thus developed was pumped across the array of thirty two SOP sensors which comprise the active, gas sensing elements of the device.

Data were analysed using a neural network which had been trained to recognise positive and negatives. Four samples which were positive for all of the clinical criteria and in which no other pathogens were found were used to train the neural network to recognise positives. Four samples which were negatives for all of the clinical criteria and in which no other pathogens were found were used to train the neural network to recognise negatives.

After training, sixteen of the seventeen remaining subjects identified as being positive by standard clinical criteria were identified as being positive by the neural network following detection of gases and volatiles, corresponding to a 94% success rate. Of the forty three subjects found to be negative by clinical criteria, thirty three were found to be negative and ten recognised as positive by the neural network. Therefore, the positive predictive value is 61.5%. It has not been determined if the subjects producing such "false positives" might eventually develop frank bacterial vaginosis.

It will be appreciated that it is not intended to limit the invention to the above examples only, many variations, such as might readily occur to one skilled in the art, being possible, without departing from the scope thereof. For example, the above described conditions might be detected from analysis of liquid samples obtained from the vaginal region of a patient. Analysis might employ analytical techniques such as GC- MS, LC or an antibody test such as an ELISA type test. Alternatively, a test might employ antibodies specific to certain diagnostic markers (such as proteins or peptides) which are coupled to an enzymatic moiety which permits amplification of the antibody- antigen interaction by releasing a specific volatile species which can be detected by a gas sensing device.

Claims

1. A method for detecting the occurrence of a condition in a female patient comprising the steps of:

detecting said gaseous or volatile substances with a gas sensing device; and

correlating the detection of said gaseous or volatile substances with the occurrence of the condition.

2. A method according to claim 1 in which the sample is obtained by applying sampling means to the vaginal region of the patient and transporting said sampling means to a gas sampling arrangement adapted to introduce gaseous or volatile substances emanating from said sampling means to said gas sensing device.

3. A method according to claim 2 in which the sampling means comprise a tampon, swab or means adapted to fit on the cervical cone.

4. A method according to claim 1 in which the gas sensing device is positioned in the vicinity of the vaginal region of the patient and said gaseous or volatile species are sampled directly by the device.

5. A method according to claim 4 in which the gas sensing device is integrated into a pair of panties or the like.

6. A method according to claim 4 in which the gas sensing device is integrated into a tampon or the like.

7. A method according to any of the previous claims in which the gas sensing device comprises at least one semiconducting organic polymer gas sensor.

8. A method according to any of the previous claims in which the gas sensing device comprises an array of gas sensors.

9. A method according to any of the previous claims in which the condition detected is cervical cancer.

10. A method according to any of claims 1 to 8 in which the condition detected is ovarian or uterian cancer.

11. A method according to any of claims 1 to 8 in which the condition detected is a viral infection.

12. A method according to claim 11 in which the viral infection comprises infection with human papilloma virus, cytomegalovirus, a STD, or HIV.

13. A method according to any of claims 1 to 8 in which the condition detected is associated with oestrus.

14. A method according to any of claims 1 to 8 in which the condition detected is a yeast infection.

15. A method according to claim 14 in which the yeast infection comprises infection with chlamydia.

16. A gas sensing system adapted to detect the occurrence of a condition in a female patient comprising: a gas sensing device; and sampling means for obtaining a sample of gaseous or volatile substances from the vaginal region of the patient and introducing said sample to said gas sensing device.

17. A gas sensing system according to claim 16 in which the gas sensing device is adapted to be positioned in the vicinity of the vaginal region of the patient and to sample directly the gaseous or volatile species.

18. A gas sensing system according to claim 17 integrated into a pair of panties of the like.

19. A gas sensing system according to claim 17 integrated into a tampon or the like.

20. A gas sensing system according to any of claims 16 to 19 in which the gas sensing device comprises at least one semiconducting organic polymer gas sensor.

21. A gas sensing system according to claim 20 in which the detection of gaseous or volatile species is indicated by a variation in the colour of the semiconducting organic polymer or polymers.

22. A gas sensing system according to any of claims 16 to 21 in which the gas sensing device comprises an array of gas sensors.